This research program focuses on the interactions of human tumor-associated antigens and lymphoid cells that lead to cytotoxic effector cells. An in vitro culture system has been established in which lymphoid cells from melanoma patients are sensitized on monolayers of autochthonous or allogeneic tumor cells. The sensitized cells have shown augmented cytotoxic activity against melanoma target cells but not against fibroblasts or other nonmelanoma tumor targets. Current efforts are concentrated on further evaluations of the specificity of this reaction by examination of other tumor systems. The nature of the effector cell will be examined. The role of T-cells, non-T lymphocytes, and phagocytic mononuclear cells will be studied. Soluble antigen preparations are currently being analyzed for the ability to generate killer cells, and the specificity of such cytotoxicity will be evaluated. The cytotoxicity generated by specific antigens will be compared to that induced by non-specific mitogens as to target cells killed and the type of effector cells involved.